Yating Ji, Junxu Hao, Xu Tao, Zhihang Li, Lijiang Chen, Na Qu
{"title":"Preparation and anti-tumor activity of paclitaxel silk protein nanoparticles encapsulated by biofilm.","authors":"Yating Ji, Junxu Hao, Xu Tao, Zhihang Li, Lijiang Chen, Na Qu","doi":"10.1080/10837450.2024.2376075","DOIUrl":"10.1080/10837450.2024.2376075","url":null,"abstract":"<p><p>In order to overcome the poor bioavailability of paclitaxel (PTX), in this study, self-assembled paclitaxel silk fibronectin nanoparticles (PTX-SF-NPs) were encapsulated with outer membrane vesicles of Escherichia coli (E. coil), and biofilm-encapsulated paclitaxel silk fibronectin nanoparticles (OMV-PTX-SF-NPs) were prepared by high-pressure co-extrusion, the size and zeta potential of the OMV-PTX-SF-NPs were measured. The antitumor effects of OMV-PTX-SF-NPs were evaluated by cellular and pharmacodynamic assays, and pharmacokinetic experiments were performed. The results showed that hydrophobic forces and hydrogen bonding played a major role in the interaction between paclitaxel and filipin proteins, and the size of OMV-PTX-SF-NPs was 199.8 ± 2.8 nm, zeta potential was -17.8 ± 1.3 mv. The cellular and in vivo pharmacokinetic assays demonstrated that the OMV-PTX-SF-NPs possessed a promising antitumor effect. Pharmacokinetic experiments showed that the AUC0-∞ of OMV-PTX-SF-NPs was 5.314 ± 0.77, which was much larger than that of free PTX, which was 0.744 ± 0.14. Overall, we have successfully constructed a stable oral formulation of paclitaxel with a sustained-release effect, which is able to effectively increase the bioavailability of paclitaxel, improve the antitumor activity, and reduce the adverse effects.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"627-638"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An overview on recent approaches for colonic drug delivery systems.","authors":"Aylin Deljavan Ghodrati, Tansel Comoglu","doi":"10.1080/10837450.2024.2362353","DOIUrl":"10.1080/10837450.2024.2362353","url":null,"abstract":"<p><p>Colon-targeted drug delivery systems have garnered significant interest as potential solutions for delivering various medications susceptible to acidic and catalytic degradation in the gastrointestinal (GI) tract or as a means of treating colonic diseases naturally with fewer overall side effects. The increasing demand for patient-friendly drug administration underscores the importance of colonic drug delivery, particularly through noninvasive methods like nanoparticulate drug delivery technologies. Such systems offer improved patient compliance, cost reduction, and therapeutic advantages. This study places particular emphasis on formulations and discusses recent advancements in various methods for designing colon-targeted drug delivery systems and their medicinal applications.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"566-581"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Burcu Uner, Juste Baranauskaite Ortasoz, Cetin Tas
{"title":"Development of thermosensitive liposome-containing in-situ gel systems for intranasal administration of thiocolchicoside and in vivo evaluation in a rabbit model.","authors":"Burcu Uner, Juste Baranauskaite Ortasoz, Cetin Tas","doi":"10.1080/10837450.2024.2364707","DOIUrl":"10.1080/10837450.2024.2364707","url":null,"abstract":"<p><strong>Aim: </strong>Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. <i>In situ</i> gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared.</p><p><strong>Method: </strong>Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. <i>In vivo</i> pharmacokinetic parameters of formulations such as C<sub>max</sub>, T<sub>max</sub>, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties.</p><p><strong>Result: </strong>Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. <i>In situ</i> liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula.</p><p><strong>Conclusion: </strong><i>In situ</i> gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"582-595"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hetal P Patel, Ayushi V Vasandia, Rahul Jha, Bhargavi V Desai, Ditixa T Desai, Praful P Dedhiya, Bhavin A Vyas, Furqan A Maulvi
{"title":"Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.","authors":"Hetal P Patel, Ayushi V Vasandia, Rahul Jha, Bhargavi V Desai, Ditixa T Desai, Praful P Dedhiya, Bhavin A Vyas, Furqan A Maulvi","doi":"10.1080/10837450.2024.2376102","DOIUrl":"10.1080/10837450.2024.2376102","url":null,"abstract":"<p><p>Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained <i>ex vivo</i> release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. <i>In vivo</i> pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (C<sub>max</sub> = 16.77 µg/g, t<sub>max</sub> = 30 min) after intranasal administration compared to intravenous administration (C<sub>max</sub> = 2.53 µg/g, t<sub>max</sub> = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain <i>via</i> olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"639-647"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Kawish, Nimra Naz Siddiqui, Humera Jahan, Abdelbari Elhissi, Hina Zahid, Bushra Khatoon, Muhammad Raza Shah
{"title":"Targeted pH-responsive delivery of rosmarinic acid <i>via</i> phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy.","authors":"Muhammad Kawish, Nimra Naz Siddiqui, Humera Jahan, Abdelbari Elhissi, Hina Zahid, Bushra Khatoon, Muhammad Raza Shah","doi":"10.1080/10837450.2024.2356210","DOIUrl":"10.1080/10837450.2024.2356210","url":null,"abstract":"<p><p>Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. <i>In vitro</i>, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC<sub>50</sub> values of (1.70 ± 0.01 μg/mL and 3.25 ± 0.14 μg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 μg/mL and 29.10 ± 0.25 μg/mL), respectively. The cellular morphology before and after treatment was further confirmed <i>via</i> inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"541-550"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shima Aliebrahimi, Amir Farnoudian-Habibi, Fatemeh Heidari, Amir Amani, Vahideh Montazeri, Shiva Sabz Andam, Reza Saber, Ali Mohammad Alizadeh, Seyed Nasser Ostad
{"title":"Using chitosan-coated magnetite nanoparticles as a drug carrier for opioid delivery against breast cancer.","authors":"Shima Aliebrahimi, Amir Farnoudian-Habibi, Fatemeh Heidari, Amir Amani, Vahideh Montazeri, Shiva Sabz Andam, Reza Saber, Ali Mohammad Alizadeh, Seyed Nasser Ostad","doi":"10.1080/10837450.2024.2372568","DOIUrl":"10.1080/10837450.2024.2372568","url":null,"abstract":"<p><p>Over the past decades, opium derivatives have been discovered as new anticancer agents. In our study, Fe<sub>3</sub>O<sub>4</sub> superparamagnetic nanoparticles (SPIONs) decorated with chitosan were loaded with papaverine or noscapine to surmount drug delivery-related obstacles. Modifying the magnetic nanoparticles (MNP) surface with polymeric materials such as chitosan prevents oxidation and provides a site for drug linkage, which renders them a great drug carrier. The obtained systems were characterized by DLS (20-40 nm were achieved for MNPs and drug- loaded MNPs), TEM (spherical with average size of 11-20 nm) FTIR, XRD, and VSM (71.3 - 42.8 emu/g). Contrary to noscapine, papaverine-MNPs attenuated 4T1 murine breast cancer cell proliferation (11.50 ± 1.74 µg/mL) effectively compared to the free drug (62.35 ± 2.88 µg/mL) while sparing L-929 fibroblast cells (138.14 ± 4.38 µg/mL). Furthermore, SPION and SPION-chitosan displayed no cytotoxic activity. Colony-formation assay confirmed the long-term cytotoxicity of nanostructures. Both developed formulations promoted ROS production accompanied by late apoptotic cell death. The biocompatible nanoparticle exerted an augmenting effect to deliver papaverine to metastatic breast cancer cells.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"596-603"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Perspective on the influence of suspension manufacturing unit operations on bioburden viability and selection of sampling points at the pilot scale.","authors":"Alicia Potuck, Johnna Webb, Jhanvee Patel","doi":"10.1080/10837450.2024.2372576","DOIUrl":"10.1080/10837450.2024.2372576","url":null,"abstract":"<p><p>The suspension wet media milling manufacturing process is a complex multi-unit operation, resulting in drug substance comminution to a target particle size. As a result of this complexity, microbial contamination is of paramount concern, particularly for suspensions dosed for parenteral use. This perspective sought to review the influence of (4) critical manufacturing unit operations using a quality risk management approach to better identify and articulate impact of each unit operation on bioburden viability. The manufacturing unit operations in scope included slurry compounding, deaeration, milling, and filling. Bow tie risk analysis was used as a visual gap analysis tool to evaluate if conventional controls were appropriate to detect and mitigate potential for microbial contamination. A deep dive into these unit operations clarified that mechanisms such as turbohypobiosis, cavitation during deaeration, high energy milling, and inert overlay may have an appreciable influence on bioburden viability and proliferation. The resultant analysis also explicated that endotoxin oversight must be closely monitored through barriers (input material controls, water quality controls) to minimize impact to the product and patient. The identified manufacturing unit operations were not appropriate as mitigating controls for endotoxin. The output of this article relates risk intersections for microbial contamination during wet media milling and offers insights in critical areas for intervention.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"618-626"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shivani Makhijani, Gehan M Elossaily, Satish Rojekar, Rahul G Ingle
{"title":"mRNA-based vaccines - global approach, challenges, and could be a promising wayout for future pandemics.","authors":"Shivani Makhijani, Gehan M Elossaily, Satish Rojekar, Rahul G Ingle","doi":"10.1080/10837450.2024.2361656","DOIUrl":"10.1080/10837450.2024.2361656","url":null,"abstract":"<p><p>mRNA-based vaccines are assured to significantly boost biopharmaceuticals since outbreak of coronavirus disease- 2019. Respiratory infections, such as influenza, SARS, MERS, COVID-19, and respiratory syncytial virus, often have high transmission rates due to their airborne spread. Respiratory infections can lead to severe illness and death. These outbreaks can cause substantial economic and social disruption, as seen with the COVID-19 pandemic. In our interconnected world, respiratory diseases can spread rapidly across borders. mRNA-based vaccines (e.g. mRNA-1283) can reduce the transmission by creating immunity in the population, thus lowering the incidence and spread of these diseases. Vaccines are crucial for global health security, helping to prevent local outbreaks from becoming global pandemics. Nevertheless, various concerns remain such as intracellular delivery, susceptibility to degradation by catalytic hydrolysis, and instability due to several physiological conditions. Therefore, an hour needed to address these challenges and opportunities for attaining high-quality and stable mRNA-based vaccines with novel drug delivery systems. The authors contributed an extensive review of the mRNA-based clinical development, progress in stability, and delivery challenges to mitigate market needs. In addition, the authors discuss crucial advances in the growth of mRNA-based vaccines to date; which dominate an extensive scope of therapeutic implementation. Finally, recent mRNA-based vaccines in clinical trials, adjuvant benefits, and prospects are discussed.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"559-565"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microsponges-mediated targeted topical delivery of rosemary oil for hair growth promotion: optimization and in-vivo studies.","authors":"Rania M Yehia, Caroline Lamie, Dalia A Attia","doi":"10.1080/10837450.2024.2372572","DOIUrl":"10.1080/10837450.2024.2372572","url":null,"abstract":"<p><p>Individuals experiencing hair loss, irrespective of gender, confront significant psychological challenges. This study explores the untapped potential of rosemary oil (ROS) to stimulate hair growth, addressing its limited permeability. The focus is on innovating ROS-loaded microsponges (MS) for enhanced topical application. Utilizing Box-Behnken design (3<sup>3</sup>), the study optimizes ROS-MS compositions by varying solvent volume, polymer mix, and drug concentration. The optimized ROS-MS formulation exhibits noteworthy attributes: a 94% ± 0.04 production yield, 99.6% ± 0.5 encapsulation efficiency, and 96.4% ± 1.6 cumulative ROS release within 24 h. These microsponges exhibit uniformity with a particle size of 14.1 µm ± 4.5. The OPT-ROSMS-gel showcases favorable characteristics in appearance, spreadability, pH, drug content, and extrudability. <i>Ex-vivo</i> skin deposition tests highlight heightened permeability of OPT-ROSMS-gel compared to pure ROS-gel, resulting in three-fold increased follicular retention. <i>In-vivo</i> studies underscore the superior efficacy of OPT-ROSMS-gel, revealing enhanced hair development in length, thickness, and bulb diameter, surpassing ROS-gel and minoxidil by approximately 1.2 and 1.5 times, respectively, along with nearly two-fold increase in β-catenin levels. In conclusion, microsponges emerge as a promising ROS delivery method, effectively addressing hair loss. This research advances hair loss treatments and underscores the significance of this innovative paradigm in fostering hair growth.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"604-617"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Aleem Mohammed, Abdulsalam A Alqahtani, Mohammed Muqtader Ahmed
{"title":"Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.","authors":"Abdul Aleem Mohammed, Abdulsalam A Alqahtani, Mohammed Muqtader Ahmed","doi":"10.1080/10837450.2024.2352491","DOIUrl":"10.1080/10837450.2024.2352491","url":null,"abstract":"<p><p>The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r<sup>2</sup> value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"517-529"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}